Manufacturing execution system for use in manufacturing baby formula

ABSTRACT

Manufacturing execution systems and methods thereof used to monitor and execute a baby formula manufacturing process are disclosed herein. Consequently, the methods and systems provide a means to perform validation and quality manufacturing on an integrated level whereby baby formula manufacturers can achieve data and product integrity and ultimately minimize cost.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/190,553 filed 29 Aug. 2008, the contents of which are fullyincorporated by reference herein.

STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH

Not applicable.

FIELD OF THE INVENTION

The invention described herein relates to the field of baby formulamanufacturing. Specifically, manufacturing execution systems and methodsused for the monitoring and execution of baby formula manufacture. Theinvention further relates to the enhancement of computer systemtechnologies and information technology to produce higher quality moreefficient baby formula thereby minimizing cost.

BACKGROUND OF THE INVENTION

Previously we have described novel methods, systems, software programs,and manufacturing execution systems for validation, quality and riskassessment, and monitoring of pharmaceutical manufacturing processes.See, US2005/0251278 published 10 Nov. 2005; US2006/0276923 published 7Dec. 2006; US2006/0271227 Published 30 Nov. 2006; US2007/0021856Published 25 Jan. 2007; and US2007/0032897 Published 8 Feb. 2007.Additionally, we endeavor to further the state of the art using softwareand computer programming in the field of baby formula manufacture.

Baby formula is a synthetic version of mothers' milk and belongs to aclass of materials known as dairy substitutes. Dairy substitutes havebeen used since the early nineteenth century for products likeoleomargarine and filled cheese. They are made by blending fats,proteins, and carbohydrates using the same technology and equipment usedto manufacture real dairy products. Since the 1940s, advances inprocessing techniques such as homogenization, fluid blending, andcontinuous batching and filling have greatly improved the ways imitationdairy products, like formula, are made. The sales of infant formulashave also improved over the last several decades. Until the early 1990s,infant formula was sold only as a pharmaceutical product. Salespeoplepresented their brands to pediatricians who would then recommend theproducts to new mothers. In 1992, federal antitrust actions resulted inmanufacturers shifting their marketing strategies toward more directmarketing techniques. Now, in addition to pharmaceutical sales,manufacturers rely heavily on direct mail campaigns and TV and printadvertising to recruit new customers. In the United States alone, theinfant formula industry is a $3 billion a year business withapproximately another $1 billion in sales outside of the United States.

Formulas are generally available in three forms: powder, liquidconcentrate, and ready-to-feed. Powder and liquid concentrate are lessexpensive but they require mixing/dilution prior to use. This may be aproblem because they may be improperly mixed or mixed with watercontaminated with bacteria. Ready-to-feed is the most expensive type butrequires no mixing before use. This is an advantage because the mothercan be sure the baby is getting the appropriate dose of nutrients anddoes not have to worry about contamination problems.

Many consumers are under the mistaken impression that the FDA closelyand carefully monitors infant formula, perhaps more scrupulously thanother foods, since infant-consumers are particularly vulnerable byvirtue of their age and total dependence on this one product. In fact,the FDA sets forth only minimal standards regarding the production andsale of synthetic milks. The mandated nutrient requirements for formulaare contained in the outdated Infant Formula Act of 1980, which waspassed by the U.S. Congress in reaction to a formula-manufacturing errorthat flooded the market with chloride-deficient formula. Today,manufacturers are required simply to include a relatively short list ofingredients and to record them on the package.

Generally, quality of infant formula is ensured at three levels, whichhave some degree of overlap. First, in the United States, there aregovernmental standards, which establish the nutritional quality ofinfant formulas and other dairy substitutes. Specific details of thesestandards can be found in the Code of Federal Regulations; moreinformation is available from the Food and Drug Administration (FDA).The FDA publishes a monograph detailing everything from the mandatednutrient list to label copy and artwork used on packaging. Second, thedairy industry sets its own industry-wide quality control standards. Theindustry is self-policing and has its own regulatory organization, theInternational Dairy Federation, which sets industry standards formanufacturing and quality control. Third, individual companies set theirown standards for quality control. For example, one producer oftriglycerides used in formula, has microbiologists and engineers monitor30 different checkpoints of triglyceride production, 24 hours a day.

As can be seen from the aforementioned, the globalization of babyformula manufacturing requires a global approach to integration keepingin mind the overall objective of strong public health protection. Toaccomplish these needed goals there is a need to carry out the followingactions. The artisan should use emerging science and data analysis toenhance validation and quality assurance programs during the babyformula manufacturing process. From the aforementioned, also apparent toone of ordinary skill in the art is the ability to provide an integratedapproach to manufacturing whereby quality and manufacturing variablesare monitored continuously during baby formula manufacture. By providingan integrated and user-friendly approach to validation and qualityassurance, the overall benefit to the public at-large is end productscontaining baby formula available at lower costs. This is turn willallow more persons to benefit from innovations that occur in themanufacturing of baby formula.

Given the current deficiencies associated with baby formula manufactureand the fact that the demand from a public health standpoint isincreasing, it becomes clear that providing an integrated systemsapproach to baby formula manufacture is desirable. Specifically,producing baby formula from a “quality by design” approach (i.e. wherequality is designed into the production versus testing qualitypost-production) is advantageous. The present invention provides thissolution.

SUMMARY OF THE INVENTION

The invention provides for manufacturing execution systems (denotedherein as manufacturing execution system or MES) and methods thereofdesigned for use in manufacturing baby formula. Specifically, softwareprograms that monitor quality control and the quality process used inthe manufacture, processing, and storing of baby formula. In certainembodiments, the software programs are used in a continuous manner toensure purity and consistency of an ingredient used in baby formulamanufacture.

The invention further comprises a software program that is fullyintegrated and automated to monitor the entire baby formulamanufacturing process.

The invention further comprises integrating a manufacturing executionsystem into a baby formula manufacturing system whereby control of thebaby formula manufacturing process is attained.

In certain embodiments, the MES is integrated into a baby formula liquidmixing system used in baby formula manufacturing.

In certain embodiments, the MES is integrated into a baby formula powderblending system used in baby formula manufacturing.

In certain embodiments, the MES is integrated into a baby formulapasteurization system used in baby formula manufacturing.

In certain embodiments, the MES is integrated into a baby formulastandardization system used in baby formula manufacturing.

In certain embodiments, the MES is integrated into a baby formulasterilization system used in baby formula manufacturing.

In certain embodiments, the MES is integrated into a packaging systemused in baby formula manufacturing.

In certain embodiments, the manufacturing execution system comprises asoftware program with a computer memory having computer readableinstructions.

In certain embodiments, the manufacturing execution system continuouslymonitors the baby formula manufacturing process.

In certain embodiments, the manufacturing execution systemsemi-continuously monitors the baby formula manufacturing process.

Based on the foregoing non-limiting exemplary embodiments, the softwareprogram can be interfaced with hardware systems or software systems ordevices to monitor quality assurance protocols put in place by thequality control unit.

The invention further comprises a manufacturing execution system whichintegrates application software and methods disclosed herein to providea comprehensive validation and quality assurance protocol that is usedby a plurality of end users whereby the data compiled from the system isanalyzed and used to determine if quality assurance protocols andvalidation protocols are being achieved.

The invention further comprises implementing the manufacturing executionsystems and software program to multiple baby formula product lineswhereby simultaneous baby formula production lines are monitored usingthe same system.

The invention further comprises implementation of the manufacturingexecution system and software program described herein into the liquidmixing, powder blending, pasteurization, homogenization,standardization, packaging, and sterilization subset of the baby formulamanufacturing process whereby the data compiled by the subset processesis tracked continuously overtime and said data is used to analyze thesubset processes and whereby said data is integrated and used to analyzethe quality control process of the baby formula manufacturing processat-large.

The invention further comprises a manufacturing execution system, whichcontrols the baby formula manufacturing process, increases productivity,and improves quality of baby formula over time.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. General Schematic of a Baby Formula Manufacturing Process. Asshown in the figure, the first step is powder blending followed byliquid mixing. The third step is pasteurization followed byhomogenization followed by standardization followed by packaging andfinally sterilization of the baby formula product. Note, depending onthe type of baby formula being manufactured, powder blending and liquidmixing may be completed concurrently.

FIG. 2. Schematic of a Manufacturing execution system integrated into aBaby formula Powder Blending and Liquid Mixing Process. As shown in thefigure, the entire baby formula powder blending and liquid mixingsystem(s) are integrated into a manufacturing execution system. Data ismonitored at critical control points to ensure quality parameters arebeing achieved. The data is monitored and analyzed on a continuousbasis. Depending on the type of baby formula that is being manufactured,the powder blending and liquid mixing system(s) may be running in thesame mixing tank concurrently.

FIG. 3. Schematic of a Manufacturing execution system integrated into aBaby Formula Pasteurization system used in baby formula manufacture. Asshown in FIG. 3A, the entire indirect pasteurization system isintegrated into the Manufacturing execution system. Data is monitored atcritical control points to ensure quality parameters are being achieved.The data is monitored and analyzed on a continuous basis. As shown inFIG. 3B, the direct pasteurization system is integrated into theManufacturing execution system. Data is monitored at critical controlpoints to ensure quality parameters are being achieved. The data ismonitored and analyzed on a continuous basis.

FIG. 4. Schematic of a Manufacturing execution system integrated into ababy formula homogenization system used in baby formula manufacture. Asshown in the figure, the entire baby formula homogenization system isintegrated into the Manufacturing execution system. Data is monitored atcritical control points to ensure quality parameters are being achieved.The data is monitored and analyzed on a continuous basis.

FIG. 5. Schematic of a Manufacturing execution system integrated into ababy formula standardization system used in baby formula manufacture. Asshown in the figure, the entire baby formula standardization system isintegrated into the Manufacturing execution system. Data is monitored atcritical control points to ensure quality parameters are being achieved.The data is monitored and analyzed on a continuous basis.

FIG. 6. Schematic of a Manufacturing execution system integrated into ababy formula packaging system used in baby formula manufacture. As shownin the figure, the entire baby formula packaging system is integratedinto the Manufacturing execution system. Data is monitored at criticalcontrol points to ensure quality parameters are being achieved. The datais monitored and analyzed on a continuous basis.

FIG. 7. Schematic of a Manufacturing execution system integrated into ababy formula sterilization system used in baby formula manufacture. Asshown in the figure, the entire baby formula sterilization system isintegrated into the Manufacturing execution system. Data is monitored atcritical control points to ensure quality parameters are being achievedbased on predetermined sterility assurance level (SAL). The data ismonitored and analyzed on a continuous basis. After sterilization, thebaby formula product is destined to shipping.

DETAILED DESCRIPTION OF THE INVENTION Outline of Sections

I.) Definitions

II.) Software Program and Computer Product

III.) Analysis

IV.) Manufacturing execution system(s)

V.) KITS/Articles of Manufacture

VI.) Background to Baby formula Manufacturing

I.) DEFINITIONS

Unless otherwise defined, all terms of art, notations and otherscientific terms or terminology used herein are intended to have themeanings commonly understood by those of skill in the art to which thisinvention pertains unless the context clearly indicates otherwise. Insome cases, terms with commonly understood meanings are defined hereinfor clarity and/or for ready reference, and the inclusion of suchdefinitions herein should not necessarily be construed to represent asubstantial difference over what is generally understood in the art.Many of the techniques and procedures described or referenced herein arewell understood and commonly employed using conventional methodology bythose skilled in the art, such as, for example, the widely utilizedcurrent Good Manufacturing Practice guidelines.

As used herein the term “baby formula” (a.k.a. infant formula, formula)means a synthetic form of mother's milk that belongs to a class ofmaterials known as dairy substitutes.

“interface” means the communication boundary between two or moreentities, such as a piece of software, a hardware device, or a user. Itgenerally refers to an abstraction that an entity provides of itself tothe outside. This separates the methods of external communication frominternal operation, and allows it to be internally modified withoutaffecting the way outside entities interact with it, as well as providemultiple abstractions of itself. It may also provide a means oftranslation between entities which do not speak the same language, suchas between a human and a computer. The interface between a human and acomputer is called a user interface. Interfaces between hardwarecomponents are physical interfaces. Interfaces between software existbetween separate software components and provide a programmaticmechanism by which these components can communicate.

“abstraction” means the separation of the logical properties of data orfunction from its implementation in a computer program.

“algorithm” means any sequence of operations for performing a specifictask.

“algorithm analysis” means a software verification and validation(“V&V”) task to ensure that the algorithms selected are correct,appropriate, and stable, and meet all accuracy, timing, and sizingrequirements.

“analog” means pertaining to data [signals] in the form of continuouslyvariable [wave form] physical quantities; e.g., pressure, resistance,rotation, temperature, voltage.

“analog device” means a device that operates with variables representedby continuously measured quantities such as pressures, resistances,rotations, temperatures, and voltages.

“analog-to-digital converter” means input related devices, whichtranslate an input device's [sensor] analog signals to the correspondingdigital signals needed by the computer.

“analysis” means a course of reasoning showing that a certain result isa consequence of assumed premises.

“application software” means software designed to fill specific needs ofa user.

“bar code” means a code representing characters by sets of parallel barsof varying thickness and separation that are read optically bytransverse scanning.

“basic input/output system” means firmware that activates peripheraldevices in a PC. Includes routines for the keyboard, screen, disk,parallel port and serial port, and for internal services such as timeand date. It accepts requests from the device drivers in the operatingsystem as well from application programs. It also contains autostartfunctions that test the system on startup and prepare the computer foroperation. It loads the operating system and passes control to it.

“benchmark” means a standard against which measurements or comparisonscan be made.

“block check” means the part of the error control procedure that is usedfor determining that a block of data is structured according to givenrules.

“bootstrap” means a short computer program that is permanently residentor easily loaded into a computer and whose execution brings a largerprogram, such an operating system or its loader, into memory.

“boundary value” means a data value that corresponds to a minimum ormaximum input, internal, or output value specified for a system orcomponent.

“boundary value analysis” means a selection technique in which test dataare chosen to lie along “boundaries” of the input domain [or outputrange] classes, data structures, procedure parameters, etc.

“branch analysis” means a test case identification technique thatproduces enough test cases such that each decision has a true and afalse outcome at least once.

“calibration” means ensuring continuous adequate performance of sensing,measurement, and actuating equipment with regard to specified accuracyand precision requirements.

“certification” means technical evaluation, made as part of and insupport of the accreditation process that establishes the extent towhich a particular computer system or network design and implementationmeet a pre-specified set of requirements.

“concept phase” means the initial phase of a software developmentproject, in which user needs are described and evaluated throughdocumentation.

“configurable, off-the-shelf software” means application software,sometimes general purpose, written for a variety of industries or usersin a manner that permits users to modify the program to meet theirindividual needs.

“control flow analysis” means a software V&V task to ensure that theproposed control flow is free of problems, such as design or codeelements that are unreachable or incorrect.

“controller” means hardware that controls peripheral devices such as adisk or display screen. It performs the physical data transfers betweenmain memory and the peripheral device.

“conversational” means pertaining to a interactive system or mode ofoperation in which the interaction between the user and the systemresembles a human dialog.

“corrective maintenance” means maintenance performed to correct faultsin hardware or software.

“critical control point” means a function or an area in a manufacturingprocess or procedure, the failure of which, or loss of control over, mayhave an adverse affect on the quality of the finished product and mayresult in an unacceptable health risk.

“data integrity” means the degree to which a collection of data iscomplete, consistent, and accurate.

“data validation” means a process used to determine if data areinaccurate, incomplete, or unreasonable. The process may include formatchecks, completeness checks, check key tests, reasonableness checks andlimit checks.

“design level” means the design decomposition of the software item;e.g., system, subsystem, program or module.

“design phase” means the period of time in the software life cycleduring which the designs for architecture, software components,interfaces, and data are created, documented, and verified to satisfyrequirements.

“diagnostic” means pertaining to the detection and isolation of faultsor failures.

“dynamic analysis” means analysis that is performed by executing theprogram code.

“encapsulation” means a software development technique that consists ofisolating a system function or a set of data and the operations on thosedata within a module and providing precise specifications for themodule.

“end user” means a person, device, program, or computer system that usesan information system for the purpose of data processing in informationexchange.

“error detection” means techniques used to identify errors in datatransfers.

“error guessing” means the selection criterion is to pick values thatseem likely to cause errors.

“error seeding” means the process of intentionally adding known faultsto those already in a computer program for the purpose of monitoring therate of detection and removal, and estimating the number of faultsremaining in the program.

“failure analysis” means determining the exact nature and location of aprogram error in order to fix the error, to identify and fix othersimilar errors, and to initiate corrective action to prevent futureoccurrences of this type of error.

“Failure Modes and Effects Analysis” means a method of reliabilityanalysis intended to identify failures, at the basic component level,which have significant consequences affecting the system performance inthe application considered.

“FORTRAN” means an acronym for FORmula TRANslator, the first widely usedhigh-level programming language. Intended primarily for use in solvingtechnical problems in mathematics, engineering, and science.

“life cycle methodology” means the use of any one of several structuredmethods to plan, design, implement, test and operate a system from itsconception to the termination of its use.

“logic analysis” means evaluates the safety-critical equations,algorithms, and control logic of the software design.

“low-level language” means the advantage of assembly language is that itprovides bit-level control of the processor allowing tuning of theprogram for optimal speed and performance. For time critical operations,assembly language may be necessary in order to generate code whichexecutes fast enough for the required operations.

“maintenance” means activities such as adjusting, cleaning, modifying,overhauling equipment to assure performance in accordance withrequirements.

“Pascal” means a high-level programming language designed to encouragestructured programming practices.

“path analysis” means analysis of a computer program to identify allpossible paths through the program, to detect incomplete paths, or todiscover portions of the program that are not on any path.

“quality assurance” means the planned systematic activities necessary toensure that a component, module, or system conforms to establishedtechnical requirements.

“quality control” means the operational techniques and procedures usedto achieve quality requirements.

“software engineering” means the application of a systematic,disciplined, quantifiable approach to the development, operation, andmaintenance of software.

“software engineering environment” means the hardware, software, andfirmware used to perform a software engineering effort.

“software hazard analysis” means the identification of safety-criticalsoftware, the classification and estimation of potential hazards, andidentification of program path analysis to identify hazardouscombinations of internal and environmental program conditions.

“software reliability” means the probability that software will notcause the failure of a system for a specified time under specifiedconditions.

“software review” means an evaluation of software elements to ascertaindiscrepancies from planned results and to recommend improvement.

“software safety change analysis” means analysis of the safety-criticaldesign elements affected directly or indirectly by the change to showthe change does not create a new hazard, does not impact on a previouslyresolved hazard, does not make a currently existing hazard more severe,and does not adversely affect any safety-critical software designelement.

“software safety code analysis” means verification that thesafety-critical portions of the design are correctly implemented in thecode.

“software safety design analysis” means verification that thesafety-critical portion of the software design correctly implements thesafety-critical requirements and introduces no new hazards.

“software safety requirements analysis” means analysis evaluatingsoftware and interface requirements to identify errors and deficienciesthat could contribute to a hazard.

“software safety test analysis” means analysis demonstrating that safetyrequirements have been correctly implemented and that the softwarefunctions safely within its specified environment.

“system administrator” means the person that is charged with the overalladministration, and operation of a computer system. The SystemAdministrator is normally an employee or a member of the establishment.

“system analysis” means a systematic investigation of a real or plannedsystem to determine the functions of the system and how they relate toeach other and to any other system.

“system design” means a process of defining the hardware and softwarearchitecture, components, modules, interfaces, and data for a system tosatisfy specified requirements.

“top-down design” means pertaining to design methodology that startswith the highest level of abstraction and proceeds through progressivelylower levels.

“validation” means establishing documented evidence which provides ahigh degree of assurance that a specific process will consistentlyproduce a product meeting its predetermined specifications and qualityattributes.

“validation, process” means establishing documented evidence whichprovides a high degree of assurance that a specific process willconsistently produce a product meeting its predetermined specificationsand quality characteristics.

“validation, prospective” means validation conducted prior to thedistribution of either a new product, or product made under a revisedmanufacturing process, where the revisions may affect the producescharacteristics.

“validation protocol” means a written plan stating how validation willbe conducted, including test parameters, product characteristics,production equipment, and decision points on what constitutes acceptabletest results.

“validation, retrospective” means validation of a process for a productalready in distribution based upon accumulated production, testing andcontrol data. Retrospective validation can also be useful to augmentinitial premarket prospective validation for new products or changedprocesses. Test data is useful only if the methods and results areadequately specific. Whenever test data are used to demonstrateconformance to specifications, it is important that the test methodologybe qualified to assure that the test results are objective and accurate.

“validation, software” means. determination of the correctness of thefinal program or software produced from a development project withrespect to the user needs and requirements. Validation is usuallyaccomplished by verifying each stage of the software development lifecycle.

“structured query language” means a language used to interrogate andprocess data in a relational database. Originally developed for IBMmainframes, there have been many implementations created for mini andmicro computer database applications. SQL commands can be used tointeractively work with a data base or can be embedded with aprogramming language to interface with a database.

“Batch” means a specific quantity of baby formula that is intended tohave uniform character and quality, within specified limits, and isproduced according to a single manufacturing order during the same cycleof manufacture.

“Component” means any ingredient intended for use in the manufacture ofbaby formula, including those that may not appear in such baby formulaproduct.

“Baby formula product” means a finished dosage form, for example,tablet, capsule, solution, powder etc. that contains an active babyformula ingredient generally, but not necessarily, in association withinactive ingredients.

“Active baby formula ingredient” means any component that is animportant dietary requirement for infants and is a primary ingredient inbaby formula. An active baby formula ingredient includes, but is notlimited to, proteins, fats, oils, vitamins, and minerals. For theavoidance of doubt, an active baby formula ingredient is not intended tobe an inactive ingredient.

“Inactive ingredient” (a.k.a. excipient) means a substance used as acarrier for the active ingredients of a baby formula product. Inaddition, excipients can be used to aid the process by which babyformula is manufactured. The active baby formula ingredient is thendissolved or mixed with an excipient. Excipients are also sometimes usedto bulk up formulations with active baby formula ingredients, to allowfor convenient and accurate dosage. Examples of excipients, include butare not limited to, thickeners, binders, starches, gums, dilutents,flavors, colors, emulsifiers, and preservatives.

“In-process material” means any material fabricated, compounded,blended, or derived by chemical reaction that is produced for, and usedin, the preparation of the baby formula product.

“Lot number, control number, or batch number” means any distinctivecombination of letters, numbers, or symbols, or any combination thereof,from which the complete history of the manufacture, processing, packing,holding, and distribution of a batch or lot of baby formula product oractive baby formula ingredient or other material can be determined.

“Quality control unit” means any person or organizational elementdesignated by the firm to be responsible for the duties relating toquality control.

“Acceptance criteria” means the product specifications andacceptance/rejection criteria, such as acceptable quality level andunacceptable quality level, with an associated sampling plan, that arenecessary for making a decision to accept or reject a lot or batch.

“manufacturing execution system” means an integrated hardware andsoftware solution designed to measure and control activities in theproduction areas of baby formula manufacturing organizations to increaseproductivity and improve quality. For the purposes of this definition anMES relates only to baby formula manufacturing processes and systems.The use of an MES of the present invention not relating to themanufacturing, storing, or production of baby formula is specificallyexcluded from the definition of an MES.

“Process analytical technology” (a.k.a. PAT) means a mechanism todesign, analyze, and control baby formula manufacturing processesthrough the measurement of critical process parameters and qualityattributes.

“Pasteurization” means the process of heating liquids for the purpose ofdestroying bacteria, protozoa, molds, and yeasts. The process was namedafter its creator, French chemist and microbiologist Louis Pasteur.

“Homogenization” means a term connoting a process that makes a mixturethe same throughout the entire substance (i.e. homogeneous). Note, forthe purposes of this definition, when soft solids are milled in aliquid, this can be seen as a form of homogenization.

“Sterilization” means any process that effectively kills or eliminatestransmissible agents (such as fungi, bacteria, viruses, prions, andspore forms, etc.) from a surface, equipment, foods, medications, babyformula, or biological culture medium. Sterilization can be achievedthrough application of heat, chemicals, irradiation, high pressure orfiltration.

II.) Software Program

The invention provides for a software program that is programmed in ahigh-level or low-level programming language, preferably a relationallanguage such as structured query language, which allows the program tointerface with an already existing program or a database. Otherprogramming languages include but are not limited to C, C++, COBOL,FORTRAN, Java, Perl, Python, Smalltalk, Dataflex, PowerBuilder, FOCUS,LINC, Oracle Reports, Quest, Ab Initio, LANSA, PL/SQL, RAMIS, S, SAS,SPSS, APE, Genexus, UNIFACE, CSS, ColdFusion, and MS visual basic.

In addition, the invention provides for a fifth-generation programminglanguage (“5GL”) based around solving problems using constraints givento the program, rather than using an algorithm written by a computerprogrammer. Essentially, a 5GL of the present invention is designed tomake the computer solve the problem (i.e. higher quality more efficientbaby formula production). This way, a programmer only needs to worryabout what problems need to be solved and what conditions need to bemet, without worrying about how to implement a routine or algorithm tosolve them. In one embodiment, a 5GL of the present invention usesProlog, OPS5, or Mercury programming language.

It will be readily apparent to one of skill in the art that thepreferred embodiment will be a software program that can be easilymodified to conform to numerous software-engineering environments. Oneof ordinary skill in the art will understand and will be enabled toutilize the advantages of the invention by designing the system withtop-down design. The level of abstraction necessary to achieve thedesired result will be a direct function of the level of complexity ofthe process that is being monitored.

The invention further comprises computer software which comprises three(3) layers. It will be appreciated by one of ordinary skill in the artthat the three (3) layers may overlap and may or may not be distinctlayers. The invention comprises a system software layer, which helps runthe computer system. The system software layer of the inventioncomprises, operating systems, device drivers, diagnostic tools, servers,windowing systems, and other utilities. The purpose of systems softwareis to insulate the applications programmer as much as possible from thedetails of the particular computer complex being used, especially memoryand other hardware features, and such as accessory devices ascommunications, printers, readers, displays, keyboards, etc.

The invention comprises computer software containing a programmingsoftware layer, which provides tools to assist a programmer to useprogramming languages in a more convenient way. These tools include butare note limited to, text editors, compilers, interpreters, linkers,debuggers, and so forth. An Integrated development environment (IDE)merges those tools into a software bundle, and a programmer may not needto type multiple commands for compiling, interpreting, debugging,tracing, and etc., especially if the IDE has an advanced graphical userinterface.

The invention comprises computer software containing an applicationsoftware layer which allows end users to accomplish one or more specific(non-computer related) tasks.

In one embodiment, the invention comprises an embedded system designedto perform one or a few dedicated functions, often with real-timecomputing constraints. It is usually embedded as part of a completedevice including hardware and mechanical parts. In a preferredembodiment, the embedded system of the invention is embedded in babyformula manufacturing hardware systems and mechanical parts.

One of ordinary skill will appreciate that to maximize results theability to amend the algorithm needed to conform to the validation andQA standards set forth by the quality control unit on each step duringbaby formula manufacture will be preferred. This differential approachto programming will provide the greatest level of data analysis leadingto the highest standard of data integrity.

The preferred embodiments may be implemented as a method, system, orprogram using standard software programming and/or engineeringtechniques to produce software, firmware, hardware, or any combinationthereof. The term “computer product” as used herein is intended toencompass one or more computer programs and data files accessible fromone or more computer-readable devices, firmware, programmable logic,memory devices (e.g. EEPROM's, ROM's, PROM's, RAM's, SRAM's, etc.)hardware, electronic devices, a readable storage diskette, CD-ROM, afile server providing access to programs via a network transmissionline, wireless transmission media, signals propagating through space,radio waves, infrared signals, etc.

The invention further provides articles (e.g., computer products)comprising a machine-readable medium including machine-executableinstructions, computer systems and computer implemented methods topractice the methods of the invention. Accordingly, the inventionprovides computers, computer systems, computer readable mediums,computer programs products and the like having recorded or storedthereon machine-executable instructions to practice the methods of theinvention. As used herein, the words “recorded” and “stored” refer to aprocess for storing information on a computer medium. A skilled artisancan readily adopt any known methods for recording information on acomputer to practice the methods of the invention.

The computer processor used to practice the methods of the invention canbe a conventional general-purpose digital computer, e.g., a personalworkstation computer, including conventional elements such asmicroprocessor and data transfer bus.

Preferably, the program will be initiated in parallel with the babyformula manufacturing process or quality assurance (“QA”) protocol. Thiswill allow the ability to monitor the baby formula manufacturing and QAprocess from its inception. However, in some instances the program canbe bootstrapped into an already existing program that will allowmonitoring from the time of execution (i.e. bootstrapped to configurableoff-the-shelf software).

For example, the critical control point for monitoring an active babyformula ingredient versus an inactive ingredient may not be equivalent.Similarly, the critical control point for monitoring an in-processmaterial may vary from component to component and often from batch tobatch.

In one embodiment, the invention provides for methods of interfacing asoftware program with a baby formula manufacturing system whereby thesoftware program is integrated into the baby formula manufacturingprocess and control of the baby formula manufacturing process isattained. The integration can be used for routine monitoring, qualitycontrol, maintenance, hazard mitigation, validation, etc.

The invention further comprises implementing the software program tomultiple devices used in baby formula manufacture to create amanufacturing execution system used to monitor and control the entirebaby formula manufacturing process.

The invention further comprises implementing the manufacturing executionsystem into multiple baby formula product lines whereby simultaneousbaby formula production lines are monitored using the same system.

The invention further comprises implementation of the manufacturingexecution system and software program described herein into the subsetof the baby formula manufacturing process whereby the data compiled bythe liquid mixing, powder blending, pasteurization, homogenization,standardization, packaging, and sterilization subset processes istracked continuously overtime and said data is used to analyze thesubset processes and whereby said data is integrated and used to analyzethe quality control process of the baby formula manufacturing processat-large.

It will also be appreciated by those skilled in the art that the varioussteps herein for baby formula production are not required to be allperformed or exist in the same production series. Thus, while in someembodiments, all steps and/or software programs and/or manufacturingexecution systems described or mentioned herein are performed or exist,in other embodiments, one or more steps are optionally, e.g., omitted,changed (in scope, order, placement, etc.) or the like. Accordingly,those of skill in the art will recognize that many modifications may bemade without departing from the scope of the present invention.

III.) Analysis

The invention provides for a method of analyzing data that is compiledas a result of the manufacturing of baby formula. Further the inventionprovides for the analysis of data that is compiled as a result of a QAprogram used to monitor the manufacture of baby formula in order tomaintain the highest level of data integrity. In one embodiment, theparameters of the data will be defined by the quality control unit.Generally, the quality control unit will provide endpoints that need tobe achieved to conform to cGMP regulations or in some instances aninternal endpoint that is more restrictive to the minimum levels thatneed to be achieved.

In a preferred embodiment, the invention provides for data analysisusing boundary value analysis. The boundary value will be set forth bythe quality control unit. Using the boundary values set forth for aparticular phase of baby formula manufacture the algorithm is defined.Once the algorithm is defined, an algorithm analysis (i.e. logicanalysis) takes place. One of skill in the art will appreciate that awide variety of tools are used to confirm algorithm analysis such as anaccuracy study processor.

One of ordinary skill will appreciate that different types of data willrequire different types of analysis. In a further embodiment, theprogram provides a method of analyzing block data via a block check. Ifthe block check renders an affirmative analysis, the benchmark has beenmet and the analysis continues to the next component. If the block checkrenders a negative, the data is flagged via standard recognition filesknown in the art and a hazard analysis and hazard mitigation occurs.

In a further embodiment, the invention provides for data analysis usingbranch analysis. The test cases will be set forth by the quality controlunit.

In a further embodiment, the invention provides for data analysis usingcontrol flow analysis. The control flow analysis will calibrate thedesign level set forth by the quality control unit, which is generatedin the design phase.

In a further embodiment, the invention provides for data analysis usingfailure analysis. The failure analysis is initiated using the failurebenchmark set forth by the quality control unit and then using standardtechniques to come to error detection. The preferred technique will betop-down. For example, error guessing based on quality control groupparameters, which are confirmed by error seeding.

In a further embodiment, the invention provides for data analysis usingpath analysis. The path analysis will be initiated after the designphase and will be used to confirm the design level. On of ordinary skillin the art will appreciate that the path analysis will be a dynamicanalysis depending on the complexity of the program modification. Forexample, the path analysis on the output of a baby formula product willbe inherently more complex that the path analysis for the validation ofan in-process material. However, one of ordinary skill will understandthat the analysis is the same, but the parameters set forth by thequality control unit will differ.

In a further embodiment, the invention provides for data analysis usingfailure modes and effects analysis. The analysis of actual or potentialfailure modes within a baby formula manufacturing system on acomponent-by-component and process by process level is analyzed forclassification or determination of a failure upon the baby formulamanufacturing system. Failures which cause any error or defects in ababy formula process, design, manufacture, or product are analyzed andcorrective action is taken during baby formula manufacture. Thecorrective action of the invention comprises modifying or stopping babyformula manufacture to obviate a failure.

In a further embodiment, the invention provides for data analysis usingroot cause analysis. The analysis occurs by identifying a root cause ofa failure or hazard with the intention of eliminating the root causethereby reducing its frequency on future baby formula batches.

In a further embodiment, the invention provides for data analysis usinghazard analysis and critical control points. The analysis occurs in asystematic preventive approach to baby formula manufacturing thataddresses physical, chemical, and biological hazards of baby formula asa means of prevention rather than finished baby formula productinspection. The analysis is used in baby formula manufacture to identifyhazards, so that key actions and locations within a baby formulamanufacturing process, known as critical control points can be taken toreduce or eliminate the risk of the hazards being realized. The analysisis used at all stages of baby formula production including liquidmixing, powder blending, pasteurization, homogenization,standardization, packaging, and sterilization. Failures which cause anyerror or defects in a baby formula process, design, manufacture, orproduct are analyzed and corrective action is taken during baby formulamanufacture. The corrective action of the invention comprises modifyingor stopping baby formula manufacture to obviate a failure.

The invention provides for a top-down design to software analysis. Thispreferred embodiment is advantageous because the parameters of analysiswill be fixed for any given process and will be set forth by the qualitycontrol unit. Thus, performing software safety code analysis thensoftware safety design analysis, then software safety requirementsanalysis, and then software safety test analysis will be preferred.

The aforementioned analysis methods are used for several non-limitingembodiments, including but not limited to, validating QA software,validating baby formula manufacturing processes and systems, andvalidating process designs wherein the integration of the system designwill allow for more efficient determination of acceptance criteria in abatch, in-process material, batch number, control number, and lot numberand allow for increased access time thus achieving a more efficientcost-saving baby formula manufacturing process.

IV. Manufacturing Execution System(s)

In one embodiment, the software program or computer product, as the casemay be, is integrated into a manufacturing execution system thatcontrols the baby formula manufacturing process. The tools of themanufacturing execution system of the invention focus on less variance,higher volumes, tighter control, and logistics of baby formulamanufacturing. One of ordinary skill in the art will understand that aMES of the invention posseses attributes to increase traceability,productivity, and quality of a baby formula product. One of ordinaryskill in the art will understand that the aforementioned attributes areachieved by monitoring such baby formula manufacturing functionsincluding, for example, equipment tracking, product genealogy, labor anditem tracking, costing, electronic signature capture, defect andresolution monitoring, executive dashboards, and other various reportingfunctions.

It will be understood by one of skill in the art that the softwareprograms or computer products integrates the hardware via generallyunderstood devices in the art (i.e. attached to the analog device via ananalog to digital converter).

The software program or computer product is integrated into themanufacturing execution system on a device-by-device basis. Aspreviously set forth, the acceptance criteria of all devices used inbaby formula manufacture for the purposes of the manufacturing executionsystem are determined by the quality control unit. The analysis of thebaby formula manufacturing occurs using any of the methods disclosedherein. (See, section III entitled “Analysis”). The program monitors andprocesses the data and stores the data using standard methods. The datais provided to an end user or a plurality of end users for assessing thequality of data generated by the device or devices. Furthermore, thedata is stored for comparative analysis to previous batches to provide arisk-based assessment in case of failure. Using the historical analysiswill provide a more streamlined baby formula manufacturing process andwill monitor to ensure that product quality is maximized. Utilizing thehistorical record will provide baby formula manufacturers an“intelligent” perspective to manufacturing. Over time, the manufacturingexecution system will teach itself and modify the baby formulamanufacturing process in a way to obviate previous failures while at thesame time continuously monitoring for new or potential failures. Inaddition, the invention comprises monitoring the data from initialprocess, monitoring the data at the end process, and monitoring the datafrom a routine maintenance schedule to ensure the system maintain dataintegrity and validation standards predetermined by the quality controlunit.

V.) Kits/Articles of Manufacture

For use in basic input/output systems, hardware calibrations, softwarecalibrations, computer systems audits, computer system securitycertification, data validation, different software system analysis,quality control, and the manufacturing of baby formula productsdescribed herein, kits are within the scope of the invention. Such kitscan comprise a carrier, package, or container that is compartmentalizedto receive one or more containers such as boxes, shrink wrap, and thelike, each of the container(s) comprising one of the separate elementsto be used in the method, along with a program or insert comprisinginstructions for use, such as a use described herein.

The kit of the invention will typically comprise the container describedabove and one or more other containers associated therewith thatcomprise materials desirable from a commercial and user standpoint,programs listing contents and/or instructions for use, and packageinserts with instructions for use.

A program can be present on or with the container. Directions and orother information can also be included on an insert(s) or program(s)which is included with or on the kit. The program can be on orassociated with the container.

The terms “kit” and “article of manufacture” can be used as synonyms.

The article of manufacture typically comprises at least one containerand at least one program. The containers can be formed from a variety ofmaterials such as glass, metal or plastic.

VI.) Background to Baby Formula Manufacturing

Baby formula is a synthetic version of mothers' milk and belongs to aclass of materials known as dairy substitutes. Dairy substitutes aremade by blending fats, proteins, and carbohydrates using the sametechnology and equipment used to manufacture real dairy products. Thedesign of infant formulas is highly complex due to the nature of thebiological requirements of the developing child. The key to successfulformula design is to match as closely as possible the physical andnutritional properties of breast milk. Milk is a natural emulsion, whichmeans it is a fine dispersion of tiny droplets of fats and oilssuspended in water. Milk also contains important components includingproteins, sugars, minerals, salts, and trace elements. Formula is madeby blending similar materials in an attempt to match the characteristicsof true milk. Formula design typically falls into one of threecategories: milk-based formula, animal or vegetable based formula, ornon-milk based.

Milk based formulas typically start with cow milk as a base since mostinfants have no problem ingesting cow's milk. This type of formula isfortified with extra nutritional elements.

Animal or vegetable-based formula is produced, mainly because someinfants have a sensitivity, allergy, or potential allergy to formulabased entirely on cow's milk. Formula made with vegetable derived milkor a limited amount of cow's milk derived components may be moresuitable for these children. Most vegetable derived formulas are soybeanbased. However, allergies to soybean milk also exist, so this approachdoes not guarantee the product will be trouble free. In general, usinghydrolyzed proteins can minimize allergy concerns. They are less likelyto cause allergic reactions.

Non-milk based formulas are expensive, specialty formulas for infantswho have a strong sensitivity to both cow's and soy milk, or othermedical or digestive conditions that are formula related.

Generally, formulas are available in three forms: powder, liquidconcentrate, and ready-to-feed. Powder and liquid concentrate are lessexpensive but they require mixing/dilution prior to use. This may be aproblem because they may be improperly mixed or mixed with watercontaminated with bacteria. Ready-to-feed is the most expensive type butrequires no mixing before use. This is an advantage because the mothercan be sure the baby is getting the appropriate dose of nutrients anddoes not have to worry about contamination problems.

In general, baby formula contains the following raw material: proteins,fats, carbohydrates, diluents, minerals, vitamins, emulsifiers, andstabilizers. As described above, protein used in formulas can come froma variety of sources such animal milk or soybeans. Soymilk is made bytaking soybeans, soaking them in baking soda, draining them, grindingthe beans, then diluting the mixture with water and homogenizing it. Theproteins, which come from soybeans, may be in the form of proteinconcentrates or protein isolates. The latter helps eliminate or reducecarbohydrates that can cause flatulence and abnormal stools. Otheruseful proteins can be derived from nuts, fish, and cottonseed oil butthese have limited application in infant formulas.

Fats and oils are an important dietary requirement for infants.Therefore, formulations attempt to match the serum fatty acid profile ofreal breast milk. These fatty acids include eicosapentaenoic acid (EPA)which may be derived from fish oil and other sources and ARA(arachidonic acid). In actual breast milk there is a significant amountof fatty compounds known as triglycerides. For example, docosahexaenoicacid (DHA) is believed to be an important triglycerides. Triglycerideswhich are similar to (but not biochemically identical to) those found inbreast milk can be derived from egg yolk phospholipids. Alternatively,fatty acid precursors (molecules that react to form dietary fatty acids)may be added to infant formula. These precursors (e.g., alpha and gammalinolenic acid) allow the infants' bodies to synthesize the necessaryfatty acids. However, this method is not as efficient for deliveringfatty acids as breast milk is.

The diluents are the carrier or bulk of the liquid of the formula. Formilk-based formulations, skim milk may be used as the primary diluents.In milk free formulations, purified water is used.

In addition, a number of essential minerals are added to infant formula.These include calcium, phosphate, sodium, potassium, chloride,magnesium; sulfur, copper, zinc, iodine, and iron. Iron is one of themost important components since all babies need a source of iron intheir diet. Some parents are concerned that iron-fortified formulascause intestinal problems in infants but this is a myth. In general,parents can expect formula fed babies to experience moregastrointestinal problems than breastfed babies.

Additionally, vitamins are added to increase the nutritional value offormula. These include vitamins A, B12, C, D, and E as well as thiamine,riboflavin, niacin, pyridoxine, pantothenate, and folacin.

Finally, a variety of materials are added to ensure the formula stayshomogenous and that the oil and water-soluble components do notseparate. These include emulsifiers such as mono and di-glycerides aswell as thickeners like natural starches and gums (e.g., suchcarrageenan.).

Using the aforementioned ingredients, the manufacturing of baby formulais completed using the following process (note, the process may bealtered depending on the type of baby formula being manufactured). Thefirst step in the process is mixing the ingredients. Generally, theprimary ingredients are blended (powder) and mixed (liquid) in largestainless steel tanks. Skim milk is then added and adjusted to about130° F.-150° F., preferably 140° F. (60° C.). Fats, oils and emulsifiersare then added. Additional heating and mixing may be required to yieldthe proper consistency set forth by the quality control unit. Inaddition, minerals, vitamins, and stabilizing gums may be added atvarious points in the process depending on their sensitivity to heat andother ingredients. Once mixing is complete, a batch is temporarilystored or transported via pipeline to pasteurization equipment.

Pasteurization is a process that protects against spoilage byeliminating bacteria, yeasts, and molds. Pasteurization involves quicklyheating and cooling the baby formula product under controlled conditionswhich microorganisms cannot survive. Generally, a temperature of185-201.2° F. (85-94° C.), held for about 30 seconds, is necessary toadequately reduce microorganisms and prepare the baby formula forfilling. Several pasteurization methods are commercially available inthe art. One common method warms the formula by sending it through atube adjacent to heat plate heat exchanger. Thus, the formula is heatedindirectly. Another method heats formula directly and then uses theheated liquid to preheat the rest of the incoming formula. The preheatedformula is further heated with steam or hot water to the pasteurizationtemperature. After pasteurization is complete, a batch is processedfurther by homogenization.

Homogenization is a process, which increases emulsion uniformity andstability by reducing the size of the fat and oil particles in the babyformula. This process can be done with a variety of mixing equipmentknown in the art, which applies high shear to the product. This type ofmixing breaks the fat and oil particles into very small droplets.

Once the baby formula has been homogenized, the next step isstandardization. During the standardization step, the resulting babyformula composition is standardized to ensure key parameters, such aspH, fat concentration, and vitamin(s) and mineral(s) are correct(generally against the previously set forth quality parameters providedby the quality control unit). If any of these ingredients are atinsufficient levels (i.e. outside quality parameters), the baby formulabatch can be reworked to achieve the appropriate levels. The batch isthen ready to be packaged.

The baby formula packaging process depends on the manufacturer and typeof equipment employed, but in general, the liquid formula is filled intometal cans which have lids crimped into place and powdered baby formulais put into plastic or paper-based containers. These can be filled onconventional liquid or powder filling equipment known in the art.

Finally, the baby formula product filled packages are subsequentlysterilized (i.e. heated and cooled to destroy any additionalmicroorganisms). The finished cans are then packed in cartons and storedfor shipping.

EXAMPLES

Various aspects of the invention are further described and illustratedby way of the several examples that follow, none of which is intended tolimit the scope of the invention.

Example 1 Utilizing the Manufacturing Execution System to Monitor a Babyformula Powder Blending and Liquid Mixing Process for Baby FormulaManufacture

Dry powder blending is one of the most widely used techniques in babyformula manufacturing. One of skill in the art will appreciate thatagitating a batch may not result in a homogeneous blend. Moreover,uniform blending may cause the ingredients to separate into layers. Itis an object of the present invention to remedy these deficiencies.

Additionally, at first glance, liquid mixing of baby formula would seemvery straightforward. One of ordinary skill in the art will appreciatethe complexities associated with liquid mixing in the baby formulamanufacturing process. For example, mixing dissimilar liquids such asoil and water or mixing chemicals that harden are problems encounteredon a daily basis. An object of the invention is to remedy thesedeficiencies.

Generally speaking and for purposes of this example, manufacturers beginwith raw materials such as proteins that come from a variety of sources,such as aminal milk or soybeans, fats, carbohydrates, dilutents,vitamins, minerals, and a variety of excipients. Depending on the typeof baby formula being made, the raw materials are mixed in either aliquid mixing or powder blending system (FIG. 2). It should be noted,that in one embodiment of the invention, the powder blending and liquidmixing processes are run on the same system. The raw materials are mixedto predetermined properties and then shipped via pipeline topasteurization systems. (FIG. 2).

In one embodiment, the Manufacturing execution system (“MES”) isintegrated into the baby formula powder blending system used in babyformula manufacture. In a further embodiment, the Manufacturingexecution system (“MES”) is integrated into the baby formula liquidmixing system used in baby formula manufacture. It will be understood byone of skill in the art that the MES integrates the hardware viagenerally understood devices in the art (i.e. attached to the analogdevice via an analog to digital converter). The MES is integrated intothe baby formula powder blending and/or liquid mixing system on adevice-by-device basis. As previously set forth, the acceptance criteriaof all devices used in the baby formula manufacture for the purposes ofthe baby formula powder blending and/or liquid mixing processes aredetermined by the quality control unit. The analysis of the software andhardware occurs using any of the methods disclosed herein. The MESmonitors and processes the data and stores the data using standardmethods. The data is provided to an end user or a plurality of end usersfor assessing the quality of data generated by the device. Furthermore,the data is stored for comparative analysis to previous batches toprovide a risk-based assessment in case of failure. Using the historicalanalysis will provide a more streamlined baby formula liquid mixingand/or powder blending process and will monitor to ensure that the babyformula powder blending and/or liquid mixing system(s) data isintegrated into subsequent baby formula manufacturing processes andsystems.

In addition, the invention comprises monitoring the data from initialliquid mixing and/or powder blending processes, monitoring the data atthe end liquid mixing and/or powder blending processes, and monitoringthe data from a routine maintenance schedule to ensure the liquid mixingand/or powder blending system(s) maintain data integrity and validationstandards predetermined by the quality control unit. (See, FIG. 2).

In one embodiment, the monitoring and analysis of the baby formulaliquid mixing and/or powder blending systems achieves a step ofintegration into a manufacturing execution system whereby manufacturingproductivity and product quality are increased. Costs are streamlinedover time.

Example 2 Utilizing the Manufacturing Execution System to Monitor aPasteurization Process for Baby Formula Manufacture

Generally speaking and for purposes of this example, pasteurization is aprocess of heating liquids for the purpose of destroying bacteria,protozoa, molds, and yeasts. Pasteurization is not intended to kill allpathogenic micro-organisms in active baby formula ingredients. Instead,pasteurization aims to reduce the number of viable pathogens so they areunlikely to cause disease (assuming, of course, that the baby formula isconsumed before its expiration date). Baby formula pasteurizationtypically uses temperatures below boiling since at temperatures abovethe boiling point for milks, casein micelles, will irreversiblyaggregate (or “curdle”). There are two (2) main types of pasteurisationused today. High Temperature/Short Time (HTST) and Extended Shelf Life(ESL) treatment. In addition, ultra-high temperature (UHT or ultra-heattreated) and Flash Pasteurization are also used for baby formulatreatment.

In the HTST process, active baby formula ingredient is forced betweenmetal plates or through pipes heated on the outside by hot water, and isheated to approximately 150° F.-167° F., preferrably approximately 161°F. for 10-25 seconds, preferrably 15-20 seconds. The HTST pasteurisationstandard was designed to achieve a 5-log reduction, killing 99.999% ofthe number of viable micro-organisms in baby formula. Generally, in theart, this is considered adequate for destroying almost all yeasts, mold,and common spoilage bacteria and also to ensure adequate destruction ofcommon pathogenic heat-resistant organisms (including Mycobacteriumtuberculosis, which causes tuberculosis and Coxiella bumetii, whichcauses Q fever). HTST pasteurization processes must be designed so thatthe active baby formula ingredients are heated evenly, and no part ofthe active baby formula ingredients are subject to a shorter time or alower temperature.

During the UHT pasteurization process the active baby formula ingredientis held at a temperature of 240° F.-260° F., preferrably 250° F. foronly a fraction of a second.

The ESL method utilizes active baby formula ingredient with a microbialfiltration step and generally lower temperatures than the HTST method.

Flash pasteurization works by rapidly heating active baby formulaingredients to a temperature of around 160-180° F. prior to the fillingand packaging processes. The active baby formula ingredient will be keptat this temperature for less than 20 seconds prior to being rapidlycooled. The flash pasteurization process has some space and costadvantages due to handling the beverage in bulk before filling.

The HTST process is a form of “indirect” pasteurization (See, FIG. 3A)because the active baby formula ingredients are sent via pipelinethrough heated plates. Conversely, “Direct” pasteurization (See, FIG.3B), which includes UHT pasteurization brings the active baby formulaingredients in direct contact with flash vapor (steam) followed by flashcooling.

In one embodiment, the MES is integrated into a baby formulapasteurization system (FIGS. 3A and 3B) used in baby formulamanufacture. It will be understood by one of skill in the art that theMES integrates the hardware via generally understood devices in the art(i.e. attached to the analog device via an analog to digital converter).The MES is integrated into the baby formula pasteurization system on adevice-by-device basis. As previously, set forth, the acceptancecriteria of all devices used in baby formula manufacture for thepurposes of pasteurization are determined by the quality control unit.The analysis of the software and hardware occurs using any of themethods disclosed herein. The MES monitors and processes the data andstores the data using standard methods. The data is provided to an enduser or a plurality of end users for assessing the quality of datagenerated by the device. Furthermore, the data is stored for comparativeanalysis to previous batches to provide a risk-based assessment in caseof failure. Using the historical analysis will provide a morestreamlined pasteurization process and will monitor to ensure that thepasteurization system data is integrated into liquid mixing and powderblending systems and other systems used in baby formula manufacture.

In addition, the invention comprises monitoring the data from initialprocess, monitoring the data at the end process, and monitoring the datafrom a routine maintenance schedule to ensure the system maintain dataintegrity and validation standard predetermined by the quality controlunit. (See, FIG. 3A and FIG. 3B).

In one embodiment, the monitoring and analysis of the pasteurizationsystems achieves a step of integration into a manufacturing executionsystem whereby manufacturing productivity and product quality areincreased. Costs are streamlined over time.

Example 3 Utilizing the Manufacturing Execution System to monitor theHomogenization Process for Baby Formula Manufacture

In the context of baby formula manufacturing, homogenization is a termconnoting a process that makes a mixture the same throughout the entiresubstance. In this case of the instant invention, the mixture is activebaby formula ingredient(s) which, in a preferred embodiment haveundergone pasteurization. For baby formula this is necessary to increaseemulsion uniformity and stability by reducing the size of the fat andoil particles in the baby formula. To achieve this, modernhomogenization technology is based on the use of pressure on liquids tosubdivide particles or droplets present in fluids into the very smallestsizes (submicron) and create a stable dispersion ideal for furtherprocessing (i.e. standardization, etc.). The passage of active babyformula product at very high pressure through a specially designed valvewith an adjustable gap, called a homogenizing valve, is able tomicrosize dispersed particles down to the order of magnitude ofmicrometers and nanometers. (FIG. 4). The fluid passes through a minutegap in the homogenizing valve. This creates conditions of highturbulence and shear, combined with compression, acceleration, pressuredrop, and impact causing the disintegration of particles and dispersionthroughout the product. After homogenization, the particles are of auniform size, typically from 0.2 to 2 micron, depending on the operatingpressure. This is an important stage in the production of baby formulaproducts. It provides improved product stability, shelf life, digestion,and taste. Homogenizing can also significantly reduce the amount ofadditives required. It prepares baby formula so that subsequent spraydrying produces the best quality of powders. This is especiallyimportant for baby formula.

The current processes or methods of homogenizing of the instantinvention can be broken down into three (3) major categories,ultrasonic, pressure, and mechanical. Ultrasonic homogenization is awidely used method to disrupt cells using ultrasonic disruption. Thesedevices work by generating intense sonic pressure waves in a liquidmedia. The pressure waves cause streaming in the liquid and, under theright conditions, rapid formation of micro-bubbles which grow andcoalesce until they reach their resonant size, vibrate violently, andeventually collapse. This phenomenon is called cavitation. The implosionof the vapor phase bubbles generates a shock wave with sufficient energyto break covalent bonds. Shear from the imploding cavitation bubbles aswell as from eddying induced by the vibrating sonic transducer disruptcells. There are several external variables which must be optimized toachieve efficient cell disruption. These variables are: tip amplitudeand intensity, temperature, cell concentration, pressure, vesselcapacity and shape.

Pressure homogenization is another widely used homogenization method.Generally, with the exception of highly filamentous microorganisms, thismethod has been found to be generally suitable for a variety ofbacteria, yeast, and mycelia. This type of homogenizer works by forcingcell suspensions through a very narrow channel or orifice underpressure. Subsequently, and depending on the type of high-pressurehomogenizer, they may or may not impinge at high velocity on ahard-impact ring or against another high-velocity stream of cells comingfrom the opposite direction. Machines which include the impingementdesign are more effective than those which do not. Disruption of thecell wall occurs by a combination of the large pressure drop, highlyfocused turbulent eddies, and strong shearing forces. The rate of celldisruption is proportional to approximately the third power of theturbulent velocity of the product flowing through the homogenizerchannel, which in turn is directly proportional to the applied pressure.Thus, the higher the pressure, the higher the efficiency of disruptionper pass through the machine. The operating parameters which affect theefficiency of high-pressure homogenizers are as follows: pressure,temperature, number of passes, valve and impingement design, and flowrate. An exemplary embodiment is set forth in FIG. 4.

Mechanical homogenization is the final type of homogenization method andcan be broken down into two (2) subcategories. Rotor-stator homogenizersand blade type homogenizers. Rotor-stator homogenizers (also calledcolloid mills) generally outperform cutting blade-type blenders and arewell suited for plant and animal tissue. Combined with glass beads, therotor-stator homogenizer has been successfully used to disruptmicroorganisms. However, the homogenized sample is contaminated withminute glass and stainless steel particles and the abrasive wear to therotor-stator homogenizer is unacceptably high. This is why thishomogenizing method is rarely used in baby formula manufacture. Celldisruption with the rotor-stator homogenizer involves hydraulic andmechanical shear as well as cavitation.

Finally, blade type homogenizers are less efficient that rotor-statorhomogenizers. In addition, many plant tissue homogenizers undergoenzymatic browning which is a biochemical oxidation process which cancomplicate subsequent separation procedures. For this reason, blade typehomogenization is not commonly used in baby formula manufacture.

In one embodiment, the pasteurized active baby formula ingredient(s)(See, Example 2 entitled “Utilizing the Manufacturing Execution Systemto monitor the Pasteurization Process for baby formula manufacture) isran through a homogenization system (See, FIG. 4). The active babyformula ingredient(s) are homogenized to the proper parameters and issent to the standardization phase. Once the product is homogenized, itis stored using standard methods in a storage tank (FIG. 4 and FIG. 5).

In one embodiment, the MES is integrated into the homogenization systemused in baby formula manufacture. It will be understood by one of skillin the art that the MES integrates the hardware via generally understooddevices in the art (i.e. attached to the analog device via an analog todigital converter). The MES is integrated into the homogenization systemon a device-by-device basis. As previously, set forth, the acceptancecriteria of all devices used in baby formula manufacture for thepurposes of the homogenization process are determined by the qualitycontrol unit. The analysis of the software and hardware occurs using anyof the methods disclosed herein. The MES monitors and processes the dataand stores the data using standard methods. The data is provided to anend user or a plurality of end users for assessing the quality of datagenerated by the device. Furthermore, the data is stored for comparativeanalysis to previous batches to provide a risk-based assessment in caseof failure. Using the historical analysis will provide a morestreamlined homogenization process and will monitor to ensure that thehomogenization system data is integrated into the homogenizationprocesses. In addition, the invention comprises monitoring the data frominitial process, monitoring the data at the end process, and monitoringthe data from a routine maintenance schedule to ensure the systemmaintain data integrity and validation standard predetermined by thequality control unit. (See, FIG. 4).

In one embodiment, the monitoring and analysis of the homogenizationsystems achieves a step of integration into a manufacturing executionsystem whereby manufacturing productivity and product quality areincreased. Costs are streamlined over time.

Example 4 Utilizing the Manufacturing Execution System to monitor aStandardization Process for Baby Formula Manufacture

Once the active baby formula ingredient(s) have been homogenized, thenext step is standardization. During the standardization step, theresulting baby formula composition is standardized to ensure keyparameters, such as pH, fat concentration, and vitamin(s) and mineral(s)are correct (generally against the previously set forth qualityparameters provided by the quality control unit). If any of theseingredients are at insufficient levels (i.e. outside quality parameters)the baby formula batch can be reworked to achieve the appropriatelevels. The batch is then ready to be packaged.

In one embodiment, the homogenized active baby formula ingredient(s)(See, Example 3 entitled “Utilizing the Manufacturing Execution Systemto monitor the Homogenization Process for baby formula manufacture) isran through a standardization system (See, FIG. 5). The active babyformula ingredient(s) are standardized to the proper parameters and issent to the packaging phase. Once the product is standardized, it isstored using standard methods in a storage tank (FIG. 5 and FIG. 6).

In one embodiment, the MES is integrated into the standardization systemused in baby formula manufacture. It will be understood by one of skillin the art that the MES integrates the hardware via generally understooddevices in the art (i.e. attached to the analog device via an analog todigital converter). The MES is integrated into the standardizationsystem on a device-by-device basis. As previously, set forth, theacceptance criteria of all devices used in baby formula manufacture forthe purposes of the standardization process are determined by thequality control unit. The analysis of the software and hardware occursusing any of the methods disclosed herein. The MES monitors andprocesses the data and stores the data using standard methods. The datais provided to an end user or a plurality of end users for assessing thequality of data generated by the device. Furthermore, the data is storedfor comparative analysis to previous batches to provide a risk-basedassessment in case of failure. Using the historical analysis willprovide a more streamlined standardization process and will monitor toensure that the standardization system data is integrated into thestandardization processes. In addition, the invention comprisesmonitoring the data from initial process, monitoring the data at the endprocess, and monitoring the data from a routine maintenance schedule toensure the system maintain data integrity and validation standardpredetermined by the quality control unit. (See, FIG. 5).

In one embodiment, the monitoring and analysis of the standardizationsystems achieves a step of integration into a manufacturing executionsystem whereby manufacturing productivity and product quality areincreased. Costs are streamlined over time.

Example 5 Utilizing the Manufacturing Execution System to monitor aPackaging Process for Baby Formula Manufacture

Packaging of active baby formula ingredient(s) are important aspects ofthe baby formula manufacturing process given that the finished babyformula product is then ultimately distributed to the consumer.Currently, the vast majority of baby formula products are administeredorally. Several alternative forms of baby formula product include butare not limited to powders, ready-made liquids, and liquids.Accordingly, the need for safe uniform packaging of baby formula productis apparent to one of skill in the art.

In one embodiment, the standardized active baby formula ingredient(s)(See, Example 4 entitled “Utilizing the Manufacturing execution systemto monitor the Standardization process for baby formula manufacture”) issent to finishing and packaging and active baby formula ingredient(s)are arranged into the proper dosage form and checked for uniformproperties (See, FIG. 6). The active baby formula ingredient(s) arefilled into the proper dosage form. (FIG. 6).

Once the baby formula product is filled and sealed the package isinspected to ensure proper sealing prior to sterilization (FIG. 7) andthen the packaged baby formula product is sent to sterilization and isthen stored using standard methods. (FIG. 6 and FIG. 7).

In one embodiment, the manufacturing execution system is integrated intothe packaging system hardware. It will be understood by one of skill inthe art that the manufacturing execution system integrates the hardwarevia generally understood devices in the art (i.e. attached to the analogdevice via an analog to digital converter).

The MES is integrated into the packaging system on a device-by-devicebasis. (FIG. 6). As previously set forth, the acceptance criteria of alldevices used in the baby formula product manufacture for the purposes ofthe packaging process are determined by the quality control unit. Theanalysis of the software and hardware occurs using any of the methodsdisclosed herein. The program monitors and processes the data and storesthe data using standard methods. The data is provided to an end user ora plurality of end users for assessing the quality of data generated bythe device. Furthermore, the data is stored for comparative analysis toprevious baby formula batches to provide a risk-based assessment in caseof failure. Using the historical analysis will provide a morestreamlined packaging process and will monitor to ensure thatingredients are mixed and packaged properly. In addition, the inventioncomprises monitoring the data from initial process, monitoring the dataat the end process, and monitoring the data from a routine maintenanceschedule to ensure the system maintain data integrity and validationstandard predetermined by the quality control unit.

In one embodiment, the monitoring and analysis of the packaging systemsachieves a step of integration into a manufacturing execution systemwhereby manufacturing productivity and product quality are increased.Costs are streamlined over time.

Example 6 Utilizing the Manufacturing Execution System to monitor aSterilization Process for Baby Formula Manufacture

Generally, and for purposes of this example, sterilization is a processthat effectively kills or eliminates transmissible agents (such asfungi, bacteria, viruses, prions, and spore forms, etc.) from babyformula product and baby formula product packaging. Sterilization can beachieved through application of heat, chemicals, irradiation, highpressure or filtration. There are generally two types of sterilization,physical and chemical.

Physical sterilization includes heat sterilization and radiationsterilization. Chemical sterilization includes the addition of chemicalsto facilitate the sterilization process. In baby formula manufacture,heat sterilization is common since it is the least invasive and babyformula is highly regulated from a quality standpoint (the end userbeing of course, infants).

Dry heat sterilization utilizes hot air that is either free from watervapour, or has very little of it, and where this moisture plays aminimal or no role in the process of sterilization. Generally, dry heatcoagulates the proteins in any organism, causes oxidative free radicaldamage, causes drying of cells, effectively killing the microorganism.General methods of dry heat sterilization include but are not limited tothe use of a hot air oven, flaming, radiation, or microwaves (See, FIG.7).

Conversely, moist heat sterilization, as the name implies, utilizes hotair that is heavily laden with water vapour and where this moistureplays the most important role in the process of sterilization. Moistheat coagulates the proteins in any organism and this is aided by thewater vapour that has a very high penetrating property, leading to theirdeath. It also causes oxidative free radical damage. This can even, athigh enough temperatures kill prions.

Sterility assurance level (SAL) is a term used in baby formulamanufacture to describe the probability of a single unit beingnon-sterile after it has been subjected to the sterilization process.For example, baby formula manufacturers design their sterilizationprocesses for an extremely low SAL-“one in a million” baby formulaproduct units should be nonsterile. SAL is also used to describe thekilling efficacy of a sterilization process, where a very effectivesterilization process has a very high SAL.

In one embodiment, the packaged baby formula product (See, Example 5entitled “Utilizing the Manufacturing execution system to monitor aPackaging process for baby formula manufacture”) is sent to asterilization process (See, FIG. 7) whereby the baby formula product isthen ready to be shipped to end users.

Once the baby formula product is sterilized within pre-determinedsterility assurance levels set forth by the quality control unit it isthen stored using standard methods. (FIG. 7).

In one embodiment, the manufacturing execution system is integrated intothe sterilization system hardware. It will be understood by one of skillin the art that the manufacturing execution system integrates thehardware via generally understood devices in the art (i.e. attached tothe analog device via an analog to digital converter).

The MES is integrated into the sterilization system on adevice-by-device basis. (FIG. 7). As previously set forth, theacceptance criteria of all devices used in the baby formula productmanufacture for the purposes of the sterilization process are determinedby the quality control unit. The analysis of the software and hardwareoccurs using any of the methods disclosed herein. The program monitorsand processes the data and stores the data using standard methods. Thedata is provided to an end user or a plurality of end users forassessing the quality of data generated by the device. Furthermore, thedata is stored for comparative analysis to previous baby formula batchesto provide a risk-based assessment in case of failure. Using thehistorical analysis will provide a more streamlined sterilizationprocess and will monitor to ensure that ingredients are mixed andpackaged properly. In addition, the invention comprises monitoring thedata from initial process; monitoring the data at the end process, andmonitoring the data from a routine maintenance schedule to ensure thesystem maintain data integrity and validation standard predetermined bythe quality control unit.

In one embodiment, the monitoring and analysis of the sterilizationsystems achieves a step of integration into a manufacturing executionsystem whereby manufacturing productivity and product quality areincreased. Costs are streamlined over time.

Example 7 Utilization of Manufacturing Execution System in CommercialBaby Formula Manufacturing Processes

The invention comprises a method for monitoring the acceptance criteriaof all components used in baby formula manufacture. The analysis of thesoftware and hardware occurs using any of the methods disclosed herein.The program monitors and processes the data and stores the data usingmethods known in the art. The data is provided to an end user or aplurality of end users for assessing the quality of the baby formulabatch. Furthermore, the data is stored for comparative analysis toprevious baby formula batches to provide a risk-based assessment in caseof failure. Using the historical analysis will provide a morestreamlined baby formula manufacturing approach and will providecost-saving over time. In addition, the invention comprises monitoringthe data from initial process, monitoring the data at the end process,and monitoring the data from a routine maintenance schedule to ensurethe system maintain data integrity and validation standard predeterminedby the quality control unit.

Example 8 Integration of the Manufacturing Execution System into a Babyformula Manufacturing Device

The invention comprises the integration of the manufacturing executionsystem into a baby formula manufacturing device. In this context, adevice used in the baby formula manufacturing process includes, but isnot limited to, blenders, bioreactors, capping machines,chromatography/separation systems, chilled water/circulating, glycol,coldrooms, clean steam, clean-in-place (CIP), compressed air, D.I./R.O.watersystems, dry heat sterilizers/ovens, fermentationequipment/bioreactors, freezers, filling equipment,filtration/purification, HVAC, environmental controls, incubators,environmentally controlled chambers, labelers, lyophilizers, dryers,mixing tanks, modular cleanrooms, neutralization systems, plant steamand condensation systems, process tanks, pressure systems, vessels,refrigerators, separation/purification equipment, specialty gas systems,steam generators/pure steam systems, steam sterilizers, stopper washers,solvent recovery systems, tower water systems, waste inactivationsystems, “kill” systems, vial inspection systems, vial washers, waterfor injection (WFI) systems, pure water systems, washers (glass, tank,carboys, etc.), centrifuges, user-independent audit trails, time-stampedaudit trails, data security, confidentiality systems, limited authorizedsystem access, electronic signatures, bar codes, dedicated systems,add-on systems, control files, Internet, LAN's, portable handhelddevices, homogenizers, sterilizers, pasteurizers, etc.

It will be understood by one of skill in the art that the manufacturingexecution system integrates the hardware via generally understooddevices in the art (i.e. attached to the analog device via an analog todigital converter).

The manufacturing execution system is integrated into the baby formulamanufacturing system on a device-by-device basis. (FIG. 2-FIG. 7). Aspreviously set forth, the acceptance criteria of all devices used in thebaby formula product manufacture for the purposes of the baby formulamanufacturing process are determined by the quality control unit. Theanalysis of the software and hardware occurs using any of the methodsdisclosed herein. The program monitors and processes the data and storesthe data using standard methods. The data is provided to an end user ora plurality of end users for assessing the quality of data generated bythe device. Furthermore, the data is stored for comparative analysis toprevious batches to provide a risk-based assessment in case of failure.Using the historical analysis will provide a more streamlined babyformula manufacturing approach and will provide cost-saving over time.In addition, the invention comprises monitoring the data from initialprocess, monitoring the data at the end process, and monitoring the datafrom a routine maintenance schedule to ensure the system maintain dataintegrity and validation standard predetermined by the quality controlunit.

Example 9 Integration of Manufacturing Execution System and AnalysisMethods into a Comprehensive Cost-Saving System

The invention comprises a manufacturing execution system integrated intoa comprehensive cost-saving baby formula manufacturing system. A user,preferably a system administrator, logs onto the system via secure means(i.e. password or other security measures known in the art) and inputsthe boundary values for a particular component of the baby formulamanufacturing process (i.e. upper and lower limits of pH, temperature,concentration, volume, blending speed, SAL, homogenization pressure,packaging unit weight, etc.) The input is at the initial stage of babyformula manufacture, the end product stage of baby formula manufacture,or any predetermined interval in between that has been established forroutine maintenance by the quality control unit. The data is generatedusing any one of the various analysis methods described herein (aspreviously stated the type of analysis used is functional to the deviceor protocol being monitored or evaluated). Subsequent to the dataanalysis, any modifications or corrective action to the baby formulamanufacturing process is implemented. The data is then stored bystandard methods known in the art. Scheduled analysis of the stored datais maintained to provide a preventative maintenance of the baby formulamanufacturing process. Over time, costs are reduced due to the trackingof data and analysis of troubled areas and frequency of hazards thatoccur on any given device in the baby formula manufacturing process. Thesystem is implemented on every device which plays a role in baby formulamanufacturing. (FIG. 2-FIG. 7). The data compiled from every device isanalyzed using the methods described herein.

Example 10 Integration of Method(s) and Program(s) into an ManufacturingExecution System (MES) Background:

A paradigm shift is needed in the way baby formula is manufactured.Current processes are not readily understood by the industry at-largeand the processes are time consuming and produce lower quality products.One of ordinary skill will appreciate that a lower quality baby formulabatch is essentially, a waste. Often the baby formula batch must be runagain using different production and system parameters. Quality controlunits that can continuously monitor a specific baby formulamanufacturing process and use that data, via data analysis methodsdisclosed herein, will allow baby formula manufacturers to producehigher quality baby formula products in a faster timeframe. Thefountainhead goal is to build quality into a baby formula product,rather than test for quality after the baby formula product is made.This Quality by Design (QbD) approach will allow one of ordinary skillin the art to understand that the former method is advantageous since itwill be easier to locate a defect in baby formula manufacturing ifmonitoring is continuous rather that post-production or post-process. Itis an object of the invention to provide this advantage.

Integration:

In one embodiment, the software program is integrated into amanufacturing execution system that controls the baby formulamanufacturing process (generally set forth in FIG. 1). It will beunderstood by one of skill in the art that the software program/computerproduct integrates the hardware via generally understood devices in theart (i.e. attached to the analog device via an analog to digitalconverter).

The software program/computer product is integrated into a manufacturingexecution system on a device-by-device basis. (FIG. 2-FIG. 7). Aspreviously set forth, the acceptance criteria of all devices used inbaby formula manufacture for the purposes of the manufacturing executionsystem are determined by the quality control unit. (FIG. 2-FIG. 7). Theanalysis of the software and hardware occurs using any of the methodsdisclosed herein. The program monitors and processes the data and storesthe data using standard methods. The data is provided to an end user ora plurality of end users for assessing the quality of data generated bythe device or devices. Furthermore, the data is stored for comparativeanalysis to previous baby formula batches to provide a risk-basedassessment in case of failure. Using the historical analysis willprovide a more streamlined baby formula manufacturing process and willmonitor to ensure that baby formula product quality is maximized. Inaddition, the invention comprises monitoring the data from initialprocess; monitoring the data at the end process, and monitoring the datafrom a routine maintenance schedule to ensure the system maintain dataintegrity and validation standards predetermined by the quality controlunit.

The present invention is not to be limited in scope by the embodimentsdisclosed herein, which are intended as single illustrations ofindividual aspects of the invention, and any that are functionallyequivalent are within the scope of the invention. Various modificationsto the models, methods, and life cycle methodology of the invention, inaddition to those described herein, will become apparent to thoseskilled in the art from the foregoing description and teachings, and aresimilarly intended to fall within the scope of the invention. Suchmodifications or other embodiments can be practiced without departingfrom the true scope and spirit of the invention.

1) A manufacturing execution system (“MES”) for use in baby formulamanufacturing by a process comprising, a) contacting a MES to aplurality of devices used in baby formula manufacturing; b) monitoringdata generated by the devices with said MES; c) analyzing the data toprovide a risk-based assessment in case of failure; d) taking correctiveaction to obviate the failure wherein said corrective action comprisesmodifying said baby formula manufacturing. 2) A method of monitoring anbaby formula manufacturing process said method comprising, a) derivingan algorithm implemented in computer-readable instructions that performsdata analysis on an baby formula manufacturing process; b) contactingsaid algorithm to a device used in baby formula manufacture; c)analyzing the data to provide a risk-based assessment in case offailure; d) taking corrective action to obviate the failure. 3) Themethod of clam 2, further comprising maintaining a historical record ofthe data analysis. 4) A method of monitoring an acceptance criteria ofan baby formula manufacturing system, said method comprising, a)monitoring data generated by an baby formula manufacturing system duringbaby formula manufacture; b) maintaining the data over time to provide ahistoric record; c) analyzing the historic record to provide acomparative analysis against an acceptance criteria; d) takingcorrective during baby formula manufacture to obviate a rejectionagainst an acceptance criteria. 5) The method of claim 4, comprisingmonitoring an acceptance criteria of a baby formula synthesis system. 6)The method of claim 4, comprising monitoring an acceptance criteria of ababy formula fermentation system. 7) The method of claim 4, comprisingmonitoring an acceptance criteria of a baby formula DNA extractionsystem. 8) The method of claim 4, comprising monitoring an acceptancecriteria of a baby formula purification system. 9) The method of claim4, comprising monitoring an acceptance criteria of a baby formulapackaging system. 10) A kit comprising the MES of claim
 1. 11) Themethod of claim 2, wherein the monitoring is continuous. 12) The methodof claim 4, wherein the monitoring is continuous. 13) The methods ofclaim 4, wherein the acceptance criteria is a sterility assurance level(“SAL”). 14) A “manufacturing execution system” adapted for use inmanufacturing baby formula comprising, a) a software system layer; b)programming software layer; and c) an application software layer. 15)The “manufacturing execution system” of claim 14, further comprising asoftware system layer using at least a device driver. 16) The“manufacturing execution system” of claim 14, further comprising aprogramming software layer using at least a compiler. 17) The“manufacturing execution system” of claim 14, further comprising anapplication system layer using at least a time stamped audit trail. 18)The MES of claim 1, wherein said devices are selected from the groupconsisting of blenders, capping machines, chromatography/separation,chilled water/circulating, coldrooms, clean steam, clean-in-place (CIP),compressed air, D.I./R.O. watersystems, dry heat sterilizers/ovens,freezers, filling equipment, filtration/purification, HVAC,environmental controls, environmentally controlled chambers, labelers,lyophilizers, dryers, mixing tanks, modular cleanrooms, neutralizationsystems, plant steam and condensation systems, process tanks, pressuresystems, vessels, refrigerators, separation/purification equipment,specialty gas systems, steam generators/pure steam systems, steamsterilizers, stopper washers, solvent recovery systems, tower watersystems, waste inactivation systems, “kill” systems, vial inspectionsystems, vial washers, water for injection (WFI) systems, pure watersystems, washers (glass, tank, carboys, etc.), centrifuges,user-independent audit trails, time-stamped audit trails, data security,confidentiality systems, limited authorized system access, electronicsignatures, bar codes, dedicated systems, add-on systems, control files,LAN's, portable handheld devices, homogenizers, sterilizers, andpasteurizers.